1. Field of the Invention
The present invention relates to carbapenem derivatives having potent antibacterial activity against a wide spectrum of bacteria. More particularly, the present invention relates to novel carbapenem derivatives having a substituted or unsubstituted imidazo[5,1-b]thiazolium-6-ylmethyl group at the 2-position of the carbapenem ring.
2. Background Art
Carbapenem derivatives, by virtue of potent antibacterial activity against a wide spectrum of bacteria, have been energetically studied as a highly useful .beta.-lactam agent, and Imipenem, Panipenem, and Meropenem have been clinically used.
Both Imipenem and Panipenem, however, are used as a mixture due to instability against renal dehydropeptidase-1 ("DHP-1") in the case of Impenem and in order to reduce nephrotoxicity in the case of Panipenem.
In recent years, research and development of carbapenem derivatives having a methyl group at the 1.beta.-position have been made for use of these compounds as a single active ingredient in preparations because they are highly stable against DHP-1. However, many of the compounds including Meropenem, which has been recently put on the market, have a pyrrolidine skeleton at the 2-position in its chemical structure. Further, they are not always satisfactory in antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and resistant Pseudomonas aeruginosa which have posed a serious clinical problem these days. Thus, a need still exists for novel carbapenem antibiotics which have improved antibacterial activity against these bacteria.
N-Onium-salt-type carbapenem derivatives having methylene at the 2-position of the carbapenem are disclosed in Japanese Patent Laid-Open No. 151191/1986. This publication, however, neither specifically describes any bicyclic heterocyclic ring in a 5+5 form nor refers to any imidazo[5,1-b]thiazole proposed in the present invention.
The present inventors have previously found that novel cephem derivatives having heterocyclic imidazo[5,1-b]thiazole at the 3-position of the cephem ring have excellent antibacterial activity against a wide spectrum of bacteria (Japanese Patent Application Nos. 230573/1993 and 211908/1994).